Abnormal cobalamin-dependent transmethylation in AIDS-associated myelopathy

Background: White matter vacuolization of the, spinal cord is common in patients with AIDS and may lead to clinical manifestations of myelopathy. The pathogenesis of AIDS-associated myelopathy (AM) is unknown and may be related to metabolic abnormalities rather than to direct HIV infection. The striking pathologic similarity between AM and the vacuolar myelopathy associated with vitamin B-12 deficiency suggests that abnormal metabolism of the B-12-dependent transmethylation pathway may be important in the pathogenesis of AM. Methods: The authors compared S-adenosylmethionine (SAM), methionine, homocysteine, and glutathione in serum and CSF of 15 patients with AM vs 13 HIV-infected controls without myelopathy (HWM). They also compared the results with a non-HIV-infected reference population (NC). All patients had normal B-12, folate, and methylmalonic acid levels. Results: There was a decrease in CSF SAM in the AM group compared with the HWM group (p<0.0001) and the NC group (p<0.0001). CSF SAM in the HWM group was also lower than that in the NC group (p=0.015). Serum methionine was also reduced in serum of the myelopathic group compared with the NC group (p=0.006). Conclusions: AM is associated with an abnormality of the vitamin B-12-dependent transmethylation pathway.